Ionizing radiation is an electromagnetic or particulate radiation capable of producing ion pairs by interaction with matter. Typical ionizing radiation includes X-rays, gamma rays, alpha particles, beta particles (electrons), neutrons, and charged nuclei. In humans, excessive radiation-induced hazards range from short term mortality (when exposed to lethal doses of radiation) to long term pathologies including carcinogenesis (when exposed to low levels of radiation over an extended period of time). Exposure to damaging or lethal ionizing radiation may occur in a variety of ways, such as in therapeutic radiology, nuclear power plant accidents, disposal of nuclear waste materials, outer space explorations by astronauts, and the potential use of nuclear weapons by terrorists or belligerent nations. Exposure from many of these situations are predictable, and therefore, modalities of prevention play an important role in radiation protection. For example, the radiation dose that is used to kill tumor tissue in a radiotherapy of cancer is now limited because of the possible lethality of normal tissue associated with higher doses. The consequences of these exposures depend upon the degree of exposure to radiation and may vary from absence of any discernable immediate effect to long-term and short-term mortality. Even though there may not be any discernable immediate or short-term effects in cases of low-level exposures, the effects may be expressed as late arising pathologies like cancer.
Although extensive research has been carried out both at the government and private sector level, only a very few drugs were identified to be effective in preventing radiation damage. These drugs, however, all have undesirable side effects that prevented their use in humans. Thus, there is still a need for a composition which is proven effective and safe in the prevention and treatment of radiation damage in humans.
In recent years, it has been recognized that the presence of free radicals may cause severe damage to the human body, since the free radicals react with important cellular components, such as DNA or the cell membrane, to diminish or impair critical cellular functions. For instance, oxygen-free radicals are implicated in many diseases including neurodegenerative diseases (ALS, Parkinson's, Alzheimer's), cataractogenesis, atherosclerosis, diabetes mellitus, ischemia-reperfusion injury, kwashiorkor, and certain toxicities, to mention only a few.
Free-radicals may be neutralized by antioxidants. One of the nutritionally provided antioxidants is vitamin E (α-tocopherol), a lipophilic oily substance that can break or prevent the propagation of free radicals in biological systems. Since radiation damage is mediated through radiation-induced free radicals, vitamin E has been used for the protection from radiation induced injuries.
For example, Weber et al [Free Radical Biology & Medicine, 22:761-769, (1997)] investigated the efficacy of topically applied tocopherols and tocotrienols in the protection of murine skin from oxidative damage induced by UV irradiation. In particular, a tocotrienol rich fraction of palm oil (TRF) was applied to mouse skin and the content of anti-oxidants (i.e., α and γ tocopherol as well as α and γ tocotrienol) before and after exposure to UV-light were measured. Weber found that prior application of the TRF to mouse skin resulted in the preservation of vitamin E in the skin [Weber et al., supra, (1997)].
U.S. Pat. No. 5,376,361 also describes a method for the prevention and/or treatment of radiation induced skin damage. The method comprises topically applying a tocotrienol or a vitamin E preparation enriched with tocotrienol to the skin. However, vitamin E is less effective as a radioprotectant when used internally.